Related Experiment Video

Updated: Jul 25, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

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Enpp1 deficiency caused chondrocyte apoptosis by inhibiting AMPK signaling pathway

Zhiqiang Gao1, Qiang Wang1, Kai Guo1

  • 1Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Rd, Shanghai, 200092, China.

Journal of Orthopaedic Surgery and Research
|June 27, 2023
PubMed
Abstract

Insights

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) deficiency causes knee osteoarthritis by increasing chondrocyte apoptosis. This is linked to the AMP-activated protein kinase (AMPK) pathway, which can be modulated by Acadesine (AICAR).

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Osteoarthritis Research

Background:

  • Ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) deficiency mimics knee osteoarthritis (OA) phenotypes.
  • The precise molecular mechanisms underlying Enpp1 deficiency-induced OA remain unclear.

Purpose of the Study:

  • To investigate the role of Enpp1 in the progression of knee OA.
  • To elucidate the molecular mechanisms by which Enpp1 deficiency contributes to OA development.

Main Methods:

  • Utilized global Enpp1-deficient (Enpp1-/-) mice and wild-type (WT) littermates.
  • Assessed chondrocyte apoptosis, proliferation, and differentiation in vitro and in vivo.
  • Performed high-throughput quantitative molecular measurements and proteomic analysis.

Main Results:

  • Enpp1-/- mice exhibited significant chondrocyte apoptosis in knee joints.
  • Enpp1 deletion inhibited AMP-activated protein kinase (AMPK) phosphorylation (P-AMPK).
  • Acadesine (AICAR), an AMPK activator, reversed Enpp1 deficiency-induced chondrocyte apoptosis and normalized P-AMPK levels.

Conclusions:

  • Enpp1 deficiency is a critical factor in knee OA pathogenesis.
  • The study identifies the AMP-activated protein kinase (AMPK) signaling pathway as a key regulator in Enpp1 deficiency-associated knee OA.
Keywords:
AICARAMPKApoptosisEnpp1Osteoarthritis

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